Asthma is the most prevalent chronic respiratory disease worldwide.1 Despite many advances in recent years, control of asthma remains poor, and many patients suffer from symptoms and exacerbations, which reduce quality of life and may result in hospital admission and even death.2 Asthma formed the focus of a number of presentations at the 28th European Respiratory Society (ERS) International Congress, which was held in Paris, France on 15–19 September 2018.
Asthma was once considered to be a single disease entity. Today, we can endotype asthma, allowing patients to receive individualised treatment. Among the most well defined endotypes is severe eosinophilic asthma (SEA), which is driven by a distinct pathophysiological process involving the abnormal production of type 2 cytokines from T-helper 2 and innate lymphoid cells.3 GlaxoSmithKline is developing the first-in-class anti-IL5 monoclonal antibody mepolizumab (Nucala®), which has demonstrated efficacy and safety in patients with SEA.4 Data from COSMEX, an open-label extension of the phase III COSMOS study, showed that the long-term safety profile (up to 4.5 years) of mepolizumab was similar to previous shorter-term trials, with no new safety signals, and provided sustained and consistent reduction of exacerbations.5
AstraZeneca presented data from the BORA phase III extension trial evaluating the long-term efficacy and safety of the anti-IL5 monoclonal antibody benralizumab (Fasenra®) as an add-on treatment in 1,926 patients with SEA who had previously completed one of the company’s previous SIROCCO or CALIMA phase III trials.6,7 Results from 793 patients show that around 75% of patients receiving benralizumab every 8 weeks remained exacerbation-free during the second year of treatment.8 Safety findings were consistent with those from SIROCCO and CALIMA,6,7 with less than 3% of patients discontinuing the study because of adverse events.8
Among AstraZeneca’s other presentation on the subject of asthma was on the development of AZD1402/PRS-060, a potent and selective blocker of the IL-4 receptor alpha, which is known to be an important component of asthma pathophysiology. AZD1402/PRS-060 is now being evaluated in clinical trials.9
In terms of mild asthma, AstraZeneca presented a post-hoc analysis of the SYGMA 1 phase III clinical trial that evaluated the short-term risk of a severe exacerbation after a single day, comparing budesonide/formoterol Symbicort® Turbuhaler® as-needed versus terbutaline Turbuhaler as-needed with or without maintenance budesonide. The use of budesonide/formoterol as-needed reduced high (>4 inhalations) reliever-use days and reduced exacerbations within the following 21 days compared with terbutaline as-needed.10
Key to the success of asthma treatment is adherence and inhaler technique, which are often suboptimal. The phase IV SPRINT study assessed the use of a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist, delivered via various inhalers including the DuoResp Spiromax® (Teva) among 1,661 patients with asthma (n=1,101) and chronic obstructive pulmonary disease (n-560). Among asthma patients, 69.6% of asthma patients reported moderate or high adherence. In addition, a high level of satisfaction with the inhaler was reported; 85.4% were “very satisfied”.11
Other presentations discussed risks associated with asthma. Obesity is a known risk factor for asthma, but new research has found that people with asthma have an elevated risk of obesity. The study was part of the European Community Respiratory Health Survey and involved 8,618 people who were not obese (body mass index <30 kg/m2) at the start of the study. Among people with asthma at the start of the study, 10.2% had become obese after 10 years, compared with 7.7% of people who did not have asthma at study onset.12,13 This finding suggests that the relationship between obesity and asthma is more complicated than previously thought, and that further research is needed to increase our understanding of the relationship.13
Another research study found that children who take paracetamol during their first 2 years of life may be at a higher risk of developing asthma by the age of 18, particularly those who had a particular variant of the glutathione S-transferase gene, GSTP1. Glutathionine is an antioxidant that removes toxins in the lungs; paracetamol consumes glutathionine, increasing the body’s exposure to toxins. It is important, however, to remember that this study only showed an association between paracetamol and asthma, and there is no evidence to suggest that paracetamol causes the condition.14,15
The impact of asthma on childhood reaches beyond its effect on wellbeing and quality of life. Another study presented at ERS has found that people who suffer with early-onset persistent asthma were three and half times more likely than children without asthma to leave school at the age of 16 with only basic education. They were twice as likely to drop out of university before completing 3 years of study and only half as likely to enter non-manual occupations. The study took place in 3 districts of Sweden in 1996; all children aged between 7–8 years were invited to participate. Participants were followed up at age 11–12, 19 and 27–28 years. By 2015, 2,291 (59%) of participants were still involved in the study. More research is needed, not only to find out why asthma is associated with reduced chances in life, but how we can provide better support these children.16,17
These diverse presentations reflect the commitment of the respiratory community to advance the understanding of asthma and develop effective strategies to manage, treat and ultimately prevent the disease.
1. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017;5:691–706.
2. Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014;24:14009.
3. de Groot JC, Ten Brinke A, Bel EH. Management of the patient with eosinophilic asthma: a new era begins. ERJ Open Res. 2015;1: pii: 00024-2015.
4. Lugogo N, Domingo C, Chanez P, et al. Long-term efficacy and safety of mepolizumab in patients with severe eosinophilic asthma: a multi-center, open-label, phase IIIb study. Clin Ther. 2016;38:2058–70.
5. Albers F, Khurana S, Bradford E, et al. Long-term safety & durability of mepolizumab in life-threatening/seriously debilitating severe eosinophilic asthma (SEA): COSMEX, Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA3566.
6. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115–27.
7. FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388:2128–41.
8. Busse WW, Bleecker ER, Fitzgerald JM, et al. Long-term safety and efficacy of benralizumab in severe, uncontrolled asthma: first results of BORA, a randomized, phase III extension study. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA2567.
9. Matschiner G, Allerdorfer A, Rattenstetter B, et al. Discovery and development of AZD1402/PRS-060 a potent and selective blocker of the IL-4 receptor alpha. Am J Respir Crit Care Med. 197:A1354.
10. O’Byrne P, Fitzgerald M, Bateman ED, et al. Risk of a severe exacerbation following higher reliever use: post-hoc analysis of SYGMA 1 in mild asthma. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France.Abstract OA1680.
11. van der Palen J, Cerveri I, Roche N, et al. DuoResp Spiromax adherence, satisfaction and ease of use: findings from a multi-country observational study in patients with asthma and COPD (SPRINT). Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract PA1020.
12. Moitra S, Carsin A-E, Abramson M, et al. Effect of asthma on the development of obesity among adults: Results of the European Community Respiratory Health Survey (ECRHS). Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA297.
13. European Respiratory Society (ERS) Press Release. People with asthma at higher risk of becoming obese. Available at: https://erscongress.org/about-ers-2018/media-centre/press-releases/143-press-releases/610-asthma-obesity.html (accessed October 4, 2018).
14. Xin D, Dharmage S, Abramson M, et al. GST genotypes modify the association between paracetamol use in early life and lung function at 18 years. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA3309.
15. European Respiratory Society (ERS) Press Release. Paracetamol use in infancy is linked to increased risk of asthma in some teenagers: specific variants in the GST genes seem to play a role in greater susceptibility to lung problems. Available at: https://erscongress.org/about-ers-2018/media-centre/press-releases/143-press-releases/613-paracetamol-infancy-use-lung-problems.html (accessed October 4, 2018).
16. European Respiratory Society (ERS) Press Release. Children with asthma are less likely to finish school and to work in non-manual occupations. Available at: https://erscongress.org/about-ers-2018/media-centre/press-releases/143-press-releases/611-children-asthma-school-work.html (accessed October 4, 2018).
17. Schyllert C, Anderson M, Lindberg A, et al. Childhood asthma affects job and education in young adults. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA298.